This Phase I SBIR is aimed at developing a simple, rapid assay to screen compounds for developmental organ toxicity using zebra fish embryos. Preliminary data using dexamethasone, which produces liver and gastrointestinal toxicity, yielded data which correlated remarkably well with data for mice and rats. Phase I research will develop simple methods to assess organ toxicity in liver and kidneys, with an overall aim of defining reproducible assay standards which may be predictive for therapeutic drug screening. A significant shortcoming of current assays is that results using one parameter have relatively low predictive value for the effects of compounds in humans, due primarily to the complexity of the toxic response. For each family of compounds, only a subset of possible enzymes or pathways is affected and different metabolites may be generated by different sets of enzymes for each compound. Phase I research will investigate genetic methods for assessing key liver and kidney enzymes as biomarkers for organ toxicity and identify genes involved in organ drug response and metabolic activation phenomenon. PROPOSED COMMERCIAL APPLICATION: By providing a rapid, high throughput method for toxicity testing, the zebrafish assay will facilitate drug screening the toxicity testingin the pharmaceutical and chemical industries.